Comment
the effect that simple interventions can have on outcome in this physiologically complex and unstable disorder. Findings from the ongoing HeadPoST trial (ClinicalTrials.gov, NCT02162017), comparing the effectiveness of the lying flat (0°) head position with the sitting up (≥30°) head position in the first 24 h of admission to hospital with acute stroke, are likely to be similarly important in this regard. Finally, the low rate of patients refusing to participate in AVERT shows that patients also see the importance of simple, pragmatic research questions. Ironically, the main barriers to more such research are those put up by agencies intended to represent the public interest: the trial regulators with their unnecessarily complex bureaucratic framework for trial performance, which often results in trial prevention, and the medical research funding agencies that in many countries have little interest in the needs of patients and clinicians for answers to pragmatic questions about making the best use of existing interventions in routine clinical practice.9 Thankfully, those agencies in Australia and the UK that funded AVERT took a different view.
Peter M Rothwell Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX2 6HE, UK [email protected] I declare no competing interests. Copyright © Rothwell. Open Access article distributed under the terms of CC BY-NC-ND. 1 2
3 4
5 6
7 8
9
Langhorne P, Williams BO, Gilchrist W, Howie K. Do stroke units save lives? Lancet 1993; 342: 395–98. The AVERT Trial Collaboration Group. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet 2015; published online April 17. http://dx.doi.org/10.1016/ S0140-6736(15)60690-0. Rothwell PM. External validity of randomised controlled trials: to whom do the results of this trial apply? Lancet 2005; 365: 82–93. Mishra NK, Diener HC, Lyden PD, Bluhmki E, Lees KR, for the VISTA Collaborators. Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke 2010; 41: 2840–48. Lynch E, Hillier S, Cadilhac D. When should physical rehabilitation commence after stroke: a systematic review. Int J Stroke 2014; 9: 468–78. Skarin M, Bernhardt J, Sjöholm A, Nilsson M, Linden T. ‘Better wear out sheets than shoes’: a survey of 202 stroke professionals’ early mobilisation practices and concerns. Int J Stroke 2011; 6: 10–15. Rothwell PM. Subgroup analysis in randomised controlled trials: importance, indications and interpretation. Lancet 2005; 365: 176–86. Manning L, Hirakawa Y, Arima H, et al. Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial. Lancet Neurol 2014; 13: 364–73. Rothwell PM. Funding for practice-oriented clinical research. Lancet 2006; 368: 262–66.
Bladder catheterisation after female genital fistula repair
www.thelancet.com Vol 386 July 4, 2015
non-inferiority margin of 10%). Additionally, no significant differences were noted in secondary outcomes of repair breakdowns 7 days after catheter removal or thereafter; urinary retention 1, 3, or 7 days
Published Online April 22, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60729-2 See Articles page 56
STR/Reuters/Corbis
In The Lancet, Mark Barone and colleagues1 report the results of their study aimed at establishing whether 7 day bladder catheterisation is non-inferior to 14 day catheterisation in terms of fistula breakdown after repair, in women with simple genital fistulas. The traditional 14 day duration of catheterisation after fistula repair has been challenged over the years, although this duration has been widely used in practice.2–4 A survey of 40 fistula surgeons by Arrowsmith and colleagues5 reported variability of postoperative catheter drainage strategies ranging from 5 to 42 days. Barone and colleagues carried out their randomised, controlled, open-label study in hospitals in eight African countries. With 261 patients in the 7 day group and 263 in the 14 day group in the study, no significant difference in fistula repair breakdown, the trial’s primary endpoint, was noted between the 7 day and 14 day bladder catheterisation groups (ten [4%] of 250 patients in the 7 day group had repair breakdown vs eight [3%] of 251 in the 14 day group, risk difference 0·8% [95% CI –2·8 to 4·5], falling within the predefined
Women recovering from fistula repair in Goma, Democratic Republic of Congo
9
Comment
after catheter removal; infections and febrile episodes potentially related to treatment; catheter blockage; extended hospital stay; and residual incontinence at 3 months. 7 day bladder drainage after repair of simple fistulas was therefore found to be non-inferior to 14 day drainage, indicating that 7 day drainage is a safe and effective way to manage postoperative bladder drainage without any substantial increase in complications. The crucial stage in wound healing, that is mobilisation of fibroblasts, granulation formation, and neovascularisation, occurs at 5 days, with inflammation generally resolving after 7 days.2,6 The findings of Barone and colleagues’ study1 will be welcome news to fistula surgeons who have agonised over the absence of capacity to care for patients, and the fact that patients with fistulas are often relegated to the bottom of theatre lists4 that are frequently loaded with emergencies. Reduction of postoperative catheterisation from 14 days to 10 days without a substantial increase in failure has been estimated to increase the number of patients with fistulas undergoing surgical repair by almost 30%3 without any increase in capital investment.3,4 Because duration of bladder catheterisation is a key determinant of the length of hospital stay, which affects treatment costs and use of hospital beds,6–9 a halving of the duration of bladder drainage would increase the turnover of women getting the opportunity for care. However, possible confounding factors such as inadequacy of consumable supplies, anaesthesia, and nursing services would need to be addressed3,4,8 for the full benefits of such a change in practice to be realised. The socioeconomic benefit of reduced hospital stay, from the perspectives of both patients and health systems, can be enormous in the setting of poorly resourced countries.4
A shortened duration of bladder drainage after simple fistula repair without an increase in the number of breakdowns is most welcome news to patients with fistulas and their caregivers. If the results of Barone and colleagues’ study can be reproduced in another multicentre randomised controlled trial, adoption of its conclusions into clinical practice would substantially expand our capacity to care for patients with fistulas. My hope is that, in the near future, obstetric fistula surgeons will have the evidence-based confidence to reduce the duration of postoperative bladder drainage without any anxiety about increased repair breakdowns. Anyetei Tonyeli Lassey Department of Obstetrics and Gynecology, Korle-Bu Teaching Hospital, PO Box KB 36, Korle-Bu, Accra, Ghana [email protected] I declare no competing interests. 1
2 3 4
5
6 7
8 9
Barone MA, Widmer M, Arrowsmith S, et al. Breakdown of simple female genital fistula repair after 7 day versus 14 day postoperative bladder catheterisation: a randomised, controlled, open-label, non-inferiority trial. Lancet 2015; published online April 22. http://dx.doi.org/S01406736(14)62337-0. Nardos R, Browning A, Member B. Duration of bladder catheterization after surgery for obstetric fistula. Int J Gynecol Obstet 2008; 103: 30–32. Nardos R, Member B, Browning A. Outcome of obstetric fistula repair after 10day versus 14-day Foley catheterization. Int J Gynecol Obstet 2012; 118: 21–23. Wall LL, Arrowsmith SD, Briggs ND, Browning A, Lassey A. The obstetric vesicovaginal fistula in the developing world. Obstet Gynecol Surv 2005; 60 (7 suppl 1): S3–S51. Arrowsmith SD, Ruminjo J, Landry EG. Current practices in treatment of female fistula: a cross-sectional study. BMC Pregnancy Childbirth 2010; 10: 73. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37: 1528–42. Frajzyngier V, Ruminjo J, Barone MA. Factors influencing urinary fistula repair outcomes in developing countries: a systematic review. Am J Obstet Gynecol 2012; 207: 248–58. Browning A, Member B. Women with obstetric fistula in Ethiopia: a 6-month follow up after surgical treatment. BJOG 2008; 115: 1564–69. Ruminjo JK, Frajzyngier V, Abdullahi MB, et al. Clinical procedures and practices used in the perioperative treatment of female genital fistula during a prospective cohort study. BMC Pregnancy Childbirth 2014; 14: 220.
Depression relapse: importance of a long-term perspective Published Online April 21, 2015 http://dx.doi.org/10.1016/ S0140-6736(14)62448-X See Articles page 63
10
Emil Kraepelin’s demarcation between dementia praecox and manic depressive illness defined affective disorder as a remitting and recurring disease. He considered that only long-term outcome was useful in assessing accuracy of diagnosis and treatment response in patients.1 The more recent interest in the outcome of single mood episodes probably indicates motives to register and
market drugs rather than assisting clinical practice. This interest has resulted in many 4–8 week randomised trials but few well designed long-term studies in patients with depression. There is now increasing evidence that Kraepelin was right. Mood disorders are generally recurring, and the relevant measure of clinical success is long-term www.thelancet.com Vol 386 July 4, 2015
the effect that simple interventions can have on outcome in this physiologically complex and unstable disorder. Findings from the ongoing HeadPoST trial (ClinicalTrials.gov, NCT02162017), comparing the effectiveness of the lying flat (0°) head position with the sitting up (≥30°) head position in the first 24 h of admission to hospital with acute stroke, are likely to be similarly important in this regard. Finally, the low rate of patients refusing to participate in AVERT shows that patients also see the importance of simple, pragmatic research questions. Ironically, the main barriers to more such research are those put up by agencies intended to represent the public interest: the trial regulators with their unnecessarily complex bureaucratic framework for trial performance, which often results in trial prevention, and the medical research funding agencies that in many countries have little interest in the needs of patients and clinicians for answers to pragmatic questions about making the best use of existing interventions in routine clinical practice.9 Thankfully, those agencies in Australia and the UK that funded AVERT took a different view.
Peter M Rothwell Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX2 6HE, UK [email protected] I declare no competing interests. Copyright © Rothwell. Open Access article distributed under the terms of CC BY-NC-ND. 1 2
3 4
5 6
7 8
9
Langhorne P, Williams BO, Gilchrist W, Howie K. Do stroke units save lives? Lancet 1993; 342: 395–98. The AVERT Trial Collaboration Group. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet 2015; published online April 17. http://dx.doi.org/10.1016/ S0140-6736(15)60690-0. Rothwell PM. External validity of randomised controlled trials: to whom do the results of this trial apply? Lancet 2005; 365: 82–93. Mishra NK, Diener HC, Lyden PD, Bluhmki E, Lees KR, for the VISTA Collaborators. Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke 2010; 41: 2840–48. Lynch E, Hillier S, Cadilhac D. When should physical rehabilitation commence after stroke: a systematic review. Int J Stroke 2014; 9: 468–78. Skarin M, Bernhardt J, Sjöholm A, Nilsson M, Linden T. ‘Better wear out sheets than shoes’: a survey of 202 stroke professionals’ early mobilisation practices and concerns. Int J Stroke 2011; 6: 10–15. Rothwell PM. Subgroup analysis in randomised controlled trials: importance, indications and interpretation. Lancet 2005; 365: 176–86. Manning L, Hirakawa Y, Arima H, et al. Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial. Lancet Neurol 2014; 13: 364–73. Rothwell PM. Funding for practice-oriented clinical research. Lancet 2006; 368: 262–66.
Bladder catheterisation after female genital fistula repair
www.thelancet.com Vol 386 July 4, 2015
non-inferiority margin of 10%). Additionally, no significant differences were noted in secondary outcomes of repair breakdowns 7 days after catheter removal or thereafter; urinary retention 1, 3, or 7 days
Published Online April 22, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60729-2 See Articles page 56
STR/Reuters/Corbis
In The Lancet, Mark Barone and colleagues1 report the results of their study aimed at establishing whether 7 day bladder catheterisation is non-inferior to 14 day catheterisation in terms of fistula breakdown after repair, in women with simple genital fistulas. The traditional 14 day duration of catheterisation after fistula repair has been challenged over the years, although this duration has been widely used in practice.2–4 A survey of 40 fistula surgeons by Arrowsmith and colleagues5 reported variability of postoperative catheter drainage strategies ranging from 5 to 42 days. Barone and colleagues carried out their randomised, controlled, open-label study in hospitals in eight African countries. With 261 patients in the 7 day group and 263 in the 14 day group in the study, no significant difference in fistula repair breakdown, the trial’s primary endpoint, was noted between the 7 day and 14 day bladder catheterisation groups (ten [4%] of 250 patients in the 7 day group had repair breakdown vs eight [3%] of 251 in the 14 day group, risk difference 0·8% [95% CI –2·8 to 4·5], falling within the predefined
Women recovering from fistula repair in Goma, Democratic Republic of Congo
9
Comment
after catheter removal; infections and febrile episodes potentially related to treatment; catheter blockage; extended hospital stay; and residual incontinence at 3 months. 7 day bladder drainage after repair of simple fistulas was therefore found to be non-inferior to 14 day drainage, indicating that 7 day drainage is a safe and effective way to manage postoperative bladder drainage without any substantial increase in complications. The crucial stage in wound healing, that is mobilisation of fibroblasts, granulation formation, and neovascularisation, occurs at 5 days, with inflammation generally resolving after 7 days.2,6 The findings of Barone and colleagues’ study1 will be welcome news to fistula surgeons who have agonised over the absence of capacity to care for patients, and the fact that patients with fistulas are often relegated to the bottom of theatre lists4 that are frequently loaded with emergencies. Reduction of postoperative catheterisation from 14 days to 10 days without a substantial increase in failure has been estimated to increase the number of patients with fistulas undergoing surgical repair by almost 30%3 without any increase in capital investment.3,4 Because duration of bladder catheterisation is a key determinant of the length of hospital stay, which affects treatment costs and use of hospital beds,6–9 a halving of the duration of bladder drainage would increase the turnover of women getting the opportunity for care. However, possible confounding factors such as inadequacy of consumable supplies, anaesthesia, and nursing services would need to be addressed3,4,8 for the full benefits of such a change in practice to be realised. The socioeconomic benefit of reduced hospital stay, from the perspectives of both patients and health systems, can be enormous in the setting of poorly resourced countries.4
A shortened duration of bladder drainage after simple fistula repair without an increase in the number of breakdowns is most welcome news to patients with fistulas and their caregivers. If the results of Barone and colleagues’ study can be reproduced in another multicentre randomised controlled trial, adoption of its conclusions into clinical practice would substantially expand our capacity to care for patients with fistulas. My hope is that, in the near future, obstetric fistula surgeons will have the evidence-based confidence to reduce the duration of postoperative bladder drainage without any anxiety about increased repair breakdowns. Anyetei Tonyeli Lassey Department of Obstetrics and Gynecology, Korle-Bu Teaching Hospital, PO Box KB 36, Korle-Bu, Accra, Ghana [email protected] I declare no competing interests. 1
2 3 4
5
6 7
8 9
Barone MA, Widmer M, Arrowsmith S, et al. Breakdown of simple female genital fistula repair after 7 day versus 14 day postoperative bladder catheterisation: a randomised, controlled, open-label, non-inferiority trial. Lancet 2015; published online April 22. http://dx.doi.org/S01406736(14)62337-0. Nardos R, Browning A, Member B. Duration of bladder catheterization after surgery for obstetric fistula. Int J Gynecol Obstet 2008; 103: 30–32. Nardos R, Member B, Browning A. Outcome of obstetric fistula repair after 10day versus 14-day Foley catheterization. Int J Gynecol Obstet 2012; 118: 21–23. Wall LL, Arrowsmith SD, Briggs ND, Browning A, Lassey A. The obstetric vesicovaginal fistula in the developing world. Obstet Gynecol Surv 2005; 60 (7 suppl 1): S3–S51. Arrowsmith SD, Ruminjo J, Landry EG. Current practices in treatment of female fistula: a cross-sectional study. BMC Pregnancy Childbirth 2010; 10: 73. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37: 1528–42. Frajzyngier V, Ruminjo J, Barone MA. Factors influencing urinary fistula repair outcomes in developing countries: a systematic review. Am J Obstet Gynecol 2012; 207: 248–58. Browning A, Member B. Women with obstetric fistula in Ethiopia: a 6-month follow up after surgical treatment. BJOG 2008; 115: 1564–69. Ruminjo JK, Frajzyngier V, Abdullahi MB, et al. Clinical procedures and practices used in the perioperative treatment of female genital fistula during a prospective cohort study. BMC Pregnancy Childbirth 2014; 14: 220.
Depression relapse: importance of a long-term perspective Published Online April 21, 2015 http://dx.doi.org/10.1016/ S0140-6736(14)62448-X See Articles page 63
10
Emil Kraepelin’s demarcation between dementia praecox and manic depressive illness defined affective disorder as a remitting and recurring disease. He considered that only long-term outcome was useful in assessing accuracy of diagnosis and treatment response in patients.1 The more recent interest in the outcome of single mood episodes probably indicates motives to register and
market drugs rather than assisting clinical practice. This interest has resulted in many 4–8 week randomised trials but few well designed long-term studies in patients with depression. There is now increasing evidence that Kraepelin was right. Mood disorders are generally recurring, and the relevant measure of clinical success is long-term www.thelancet.com Vol 386 July 4, 2015
